Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules

Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate di...

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Main Authors: Cecilia B. Michalowski, Marcelo D. Arbo, Louise Altknecht, Andréia N. Anciuti, Angélica S. G. Abreu, Luciana M. R. Alencar, Adriana R. Pohlmann, Solange C. Garcia, Sílvia S. Guterres
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/12/1/80
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author Cecilia B. Michalowski
Marcelo D. Arbo
Louise Altknecht
Andréia N. Anciuti
Angélica S. G. Abreu
Luciana M. R. Alencar
Adriana R. Pohlmann
Solange C. Garcia
Sílvia S. Guterres
author_facet Cecilia B. Michalowski
Marcelo D. Arbo
Louise Altknecht
Andréia N. Anciuti
Angélica S. G. Abreu
Luciana M. R. Alencar
Adriana R. Pohlmann
Solange C. Garcia
Sílvia S. Guterres
author_sort Cecilia B. Michalowski
collection DOAJ
description Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from &#8722;14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (<i>p</i> &lt; 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.
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spelling doaj.art-90ae1a1c2cff474685208c68dbfd9ced2022-12-22T04:01:19ZengMDPI AGPharmaceutics1999-49232020-01-011218010.3390/pharmaceutics12010080pharmaceutics12010080Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core NanocapsulesCecilia B. Michalowski0Marcelo D. Arbo1Louise Altknecht2Andréia N. Anciuti3Angélica S. G. Abreu4Luciana M. R. Alencar5Adriana R. Pohlmann6Solange C. Garcia7Sílvia S. Guterres8Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, BrazilLaboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre 90610-000, BrazilInstituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre 90035-003, BrazilLaboratório de Microscopia Avançada, Departamento de Física, Universidade Federal do Ceara, Campus do Pici, Fortaleza 60455-900, BrazilLaboratório de Microscopia Avançada, Departamento de Física, Universidade Federal do Ceara, Campus do Pici, Fortaleza 60455-900, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, BrazilMulti-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from &#8722;14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (<i>p</i> &lt; 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.https://www.mdpi.com/1999-4923/12/1/80lipid-core nanocapsulesantihypertensivesurface-functionalizationcaptoprilfurosemidetoxicityoral drug delivery
spellingShingle Cecilia B. Michalowski
Marcelo D. Arbo
Louise Altknecht
Andréia N. Anciuti
Angélica S. G. Abreu
Luciana M. R. Alencar
Adriana R. Pohlmann
Solange C. Garcia
Sílvia S. Guterres
Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
Pharmaceutics
lipid-core nanocapsules
antihypertensive
surface-functionalization
captopril
furosemide
toxicity
oral drug delivery
title Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
title_full Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
title_fullStr Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
title_full_unstemmed Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
title_short Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
title_sort oral treatment of spontaneously hypertensive rats with captopril surface functionalized furosemide loaded multi wall lipid core nanocapsules
topic lipid-core nanocapsules
antihypertensive
surface-functionalization
captopril
furosemide
toxicity
oral drug delivery
url https://www.mdpi.com/1999-4923/12/1/80
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